Recent Studies : Adherence

In the treatment of Ph+ CML with TKI therapy, 2 recent clinical trials have shown that adherence to oral therapy is critical to achieving and maintaining optimal response.^1,2 In fact, evidence demonstrates that missing more than 2 or 3 daily doses each month can negatively impact response.^1,2 Here is a summary of the results from the Hammersmith study and the ADAGIO study.

THE HAMMERSMITH STUDY¹

Study design

• 87 patients completed the study
• Patients had achieved complete cytogenetic response (CCyR), had chronic-phase Ph+ CML, and had received oral therapy for at least 2 years
• Adherence was monitored over 90 days

Key findings

• Adherence rate (>90% or ≤90%) was strongly associated with the 6-year probability of MMR (Figure 1), 4-log reduction in BCR-ABL, complete molecular response (CMR), and response at 18 months
  
  Figure 1: 6-Year Probability of MMR by Adherence Rate
  
  
  
  
  

  Please click on the image to enlarge it

  Reproduced from Marin et al.¹
  • Probability of MMR for the 23 patients with an adherence rate ≤90% was 13.9%, while for the 64 patients with an adherence rate >90% it was 93.7% (P<0.001)¹
• Almost all patients who missed fewer than 3 daily doses each month achieved MMR¹
  • Only 1 in 7 patients who missed at least 3 daily doses each month achieved MMR¹
  • No patient who missed at least 6 daily doses each month achieved MMR¹
  • Almost half of patients who missed fewer than 3 daily doses each month achieved CMR; no patient who missed at least 3 daily doses each month achieved CMR¹
• Adherence was poor after dose increase to greater than 400 mg per day¹
• Adherence rate and hOCT1 transcript level were the only 2 independent predictors of MMR and 4-log reduction; adherence rate was the only independent predictor of CMR¹

Additional findings¹

• Young patients were more likely to have a lower adherence rate
• Unexplained 5-fold increases in BCR-ABL1 transcript levels were predictive of poor adherence
• Low adherence was common in patients suffering from adverse effects—healthcare providers should regularly ask patients if they are experiencing adverse effects

Conclusions¹

• Adherence is the critical factor for achieving molecular responses; adherence rate was the only independent factor that predicted CMR
• No CMR was observed when adherence was ≤90%; no MMR was observed when adherence was ≤80%. 90% adherence is equivalent to missing 2 to 3 tablets per month

THE ADAGIO STUDY²

Study design

• 169 patients completed the study
• Patients had chronic-phase CML for an average of 4 years and were receiving oral therapy
• Adherence (taking medicine every day as directed by the physician) was evaluated over 90 days

Results

• More patients failed to adhere to therapy than they, their physicians, and their family members realized
• Failure to adhere was related to the patient, physician-patient relationship, and treatment center
• Adherence greatly influenced response, as demonstrated in Figure 2 below
  
  Figure 2: Response Achieved by Adherence Rate
  
  
  
  
  

  Please click on the image to enlarge it

  Adapted from Noens et al.²
  
  • Patients with suboptimal responses missed at least 7 daily doses each month, whereas patients with optimal responses missed only 1 or 2 daily doses each month²
  • Patients who failed to achieve CCyR missed at least 7 daily doses each month, whereas patients who achieved CCyR missed only about 3 daily doses each month²
• Patients who function well and those who have taken oral CML therapy for a long time may become more lax about taking their medication²

Next: Tips to Improve Patient Adherence

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